The sites of production and storage of plasminogen will be studied in the cat after depletion of circulating plasminogen by streptokinase (SK) injection. A plasmin substance which appears after depletion and stimulates plasminogen production in cross-injected animals will also be studied. SK, which activates human plasminogen by a complicated mechanism, undergoes changes during the reaction. We will study the successive changes by gel electrophoresis, ultracentrifugal analysis and biochemical reactions to determine if SK derivatives possess biological (and possible therapeutic) value. The naturally occurring system in the blood for activating plasminogen in man will be studied with the help of a new, highly sensitive plasmin assay which we have developed. Virtually nothing is known as to how the body mobilizes its defense against a thrombus. If this system could be adequately stimulated, it would provide a powerful tool for the dissolving of blood clots.